Glioblastomas (GBMs) are the most frequent primary malignancies in the central nervous system. Aberrant activation of WNT/β-catenin signaling pathways is critical for GBM malignancy. However, the regulation of WNT/β-catenin signaling cascades remains unclear. Presently, we observed the increased expression of ZEB2 and the decreased expression of miR-637 in GBM. The expression of miR-637 was negatively correlated with ZEB2 expression. miR-637 overexpression overcame the ZEB2-enhanced cell proliferation and G1/S phase transition. Besides, miR-637 suppressed the canonical WNT/β-catenin pathways by targeting WNT7A directly. Gain- and loss-of-function experiments with U251 mice demonstrated that miR-637 inhibited cell proliferation and arrested the G1/S phase transition, leading to tumor growth suppression. The collective findings suggest that ZEB2 and WNT/β-catenin cascades merge at miR-637, and the ectopic expression of miR-637 disturbs ZEB2/WNT/β-catenin-mediated GBM growth. The findings provide new clues for improving β-catenin-targeted therapy against GBM.

胶质母细胞瘤 (GBM) 是中枢神经系统中最常见的原发性恶性肿瘤。WNT/β-连环蛋白信号通路的异常激活对 GBM 恶性肿瘤至关重要。然而，WNT/β-连环蛋白信号级联的调控仍不清楚。目前，我们观察到 GBM 中 ZEB2 的表达增加和 miR-637 的表达减少。miR-637的表达与ZEB2的表达呈负相关。miR-637 过表达克服了 ZEB2 增强的细胞增殖和 G1/S 期转变。此外，miR-637 通过直接靶向 WNT7A 来抑制经典的 WNT/β-catenin 通路。U251 小鼠的功能获得和功能丧失实验表明，miR-637 抑制细胞增殖并阻止 G1/S 期转变，从而抑制肿瘤生长。集体研究结果表明 ZEB2 和 WNT/β-连环蛋白级联在 miR-637 处合并，并且 miR-637 的异位表达干扰了 ZEB2/WNT/β-连环蛋白介导的 GBM 生长。这些发现为改进针对 GBM 的 β-catenin 靶向治疗提供了新的线索。